Assay for and uses of peptide hormone receptor agonists

The invention features a method for determining whether a candidate compound is a non-peptide agonist of a peptide hormone receptor. In this method, a candidate compound is exposed to a form of the peptide hormone receptor, or to a protein that interacts with a peptide hormone receptor, which has an enhanced ability to amplify the intrinsic activity of a non-peptide agonist. The second messenger signaling activity of the enhanced receptor is measured in the presence of the candidate compound, and compared to the second messenger signaling activity of the wildtype receptor measured in the absence of the candidate compound. A change in second messenger signaling activity indicates that the candidate compound is an agonist. An increase in second messenger signaling activity indicates that the compound is either a full or partial positive agonist; a decrease in second messenger signaling activity indicates that the compound is an inverse (also termed a ‘negative’) agonist. The invention further embraces a method of using a peptide hormone receptor agonist for the treatment or prevention of a physiological disease, as well as particular enhanced receptors and the nucleic acid sequences which code for them.